DRD2 Polymorphisms Imparting Risk for Schizophrenia

Schizophrenia is a disorder that affects 1% of the population and causes enormous deficits in functioning. The development of this disorder is through unclear mechanisms, yet studies suggest that genetics and dopamine processes play a major role in the manifestation of schizophrenia. This study considers the gene that encodes dopamine receptor D2 (DRD2) and how single nucleotide polymorphisms (SNPs) affect alternative splicing of the gene and the balance between the two different protein isoforms, Long (D2L) and Short (D2S). Four mutations (rs12363125 and rs2511521 from intron 5 and rs6275 and rs6277 from exon 7) were studied. Constructs were derived from extracted DNA from postmortem brain tissue of Brodmann’s Area 10 of deceased patients with schizophrenia and non-psychiatric comparison subjects. Enzyme digests and ligations of patient DNA were used to create constructs that have a spectrum of mutation combinations. Quantitative polymerase chain reaction (qPCR) analysis was used to measure the proportional expression of the different isoforms. A linear regression model with an r2of 0.255 showed that more than 25% of the variance in D2L to D2S expression ratios (L/S Ratios) were attributable to SNPs, and rs6275 and rs6277 were found to independently and significantly affect L/S Ratios expressed by cells, with

Lymphatic expression of CLEVER-1 in breast cancer and its relationship with lymph node metastasis

BACKGROUND Mechanisms regulating breast cancer lymph node metastasis are unclear. Staining of CLEVER-1 (common lymphatic endothelial and vascular endothelial receptor-1) in human breast tumors was used, along with in vitro techniques, to assess involvement in the metastatic process. METHODS 148 sections of primary invasive breast cancers, with 10 yr follow-up, were stained with anti-CLEVER-1. Leukocyte infiltration was assessed, along with involvement of specific subpopulations by staining with CD83 (mature dendritic cells, mDC), CD209 (immature DC, iDC) and CD68 (macrophage, Mϕ). In vitro expression of CLEVER-1 on lymphatic (LEC) and blood endothelial cells (BEC) was examined by flow cytometry. RESULTS In vitro results showed that although both endothelial cell types express CLEVER-1, surface expression was only evident on LEC. In tumour sections CLEVER-1 was expressed in blood vessels (BV, 61.4% of samples), lymphatic vessels (LV, 18.2% of samples) and in Mϕ/DCs (82.4% of samples). However, only CLEVER-1 expression in LV was associated with LN metastasis (p = 0.027) and with Mϕ indices (p = 0.021). Although LV CLEVER-1 was associated with LN positivity there was no significant correlation with recurrence or overall survival, BV CLEVER-1 expression was, however, associated with increased risk of recurrence (p = 0.049). The density of inflammatory infiltrate correlated with CLEVER-1 expression in BV (p < 0.001) and LV (p = 0.004). CONCLUSIONS The associations between CLEVER-1 expression on endothelial vessels and macrophage/leukocyte infiltration is suggestive of its regulation by inflammatory conditions in breast cancer, most likely by macrophage-associated cytokines. Its upregulation on LV, related surface expression, and association with LN metastasis suggest that it may be an important mediator of tumor cell metastasis to LN

Preparing Instructional Leaders: Evaluating a Regional Program to Gauge Perceived Effectiveness

An instructional leadership program (ILP) has offered education and support to three cohorts of educational leaders in Nova Scotia, Canada, amounting to approximately 130 participants. Quantitative and qualitative feedback from a convenience sample (n = 90) suggests that the ILP offers an extremely useful practical program; in fact, 95 percent of the sample indicates advances in the categories of professional growth, improved instructional leadership, and tangible progress in administrative effectiveness. Systemic and school environment trends have dictated that educational leaders need a skill set that positions them to respond more aptly to issues of poverty, socioemotional health, and mental health while attending to improved community building both within the school and in the greater public. This study uses surveys, interviews, and focus groups to identify emerging and impending challenges

Quantifying the Impact of Water Abstraction for Low Head ‘Run of the River’ Hydropower on Localized River Channel Hydraulics and Benthic Macroinvertebrates

‘Run of the river’ (ROR) hydropower schemes have undergone a recent resurgence in Europe, and with legislation requiring the protection and enhancement of the physical and ecological condition of European rivers, there is a need to understand the impacts of these schemes. This paper presents an assessment of the eco-hydraulic impact of a ROR hydropower scheme in the Peak District National Park, UK. Due to the ponded nature of the depleted stretch at the study site, this paper focuses on the characterization of the hydraulic impact of water abstraction for a ROR scheme at the hydropower outlet and samples microhabitats of benthic macroinvertebrates within the hydraulically affected zones. Measurement of hydraulic transects shows that the scheme's operation notably alters river channel hydraulics at 60% of water depth, whilst impacts are much less distinct in close proximity to the river bed. We identify eco-hydraulic relationships between benthic macroinvertebrate communities and localized near-bed velocity and turbulence conditions, thus indicating the potential for water abstraction by ROR schemes to impact lower trophic levels of riverine ecosystems. However, spatial patch-scale (10–100 m2) meso-habitat comparisons of invertebrate communities around the hydropower outlet showed only subtle differences, suggesting that in this case benthic communities are only minimally impacted by the ROR scheme